Prediction Model for Radiation Sensitivity in Children with Cancer

描述(由申请人提供)：儿童癌症幸存者在另一个部位继发恶性肿瘤的风险增加。先前在儿童癌症存活者研究(CCSS)中的研究表明，最常见的第二种恶性肿瘤是基底细胞癌(BCC)，而基底细胞癌最重要的危险因素是暴露于治疗性放射。这些数据与普通人群中发生的基底细胞癌病例形成对比，后者的关键风险因素是阳光照射和肤色。虽然很明显，治疗性辐射暴露会增加儿童癌症幸存者患BCC的风险，但许多人暴露在辐射中，不会发展为BCC。因此，为了解决这种个体间的差异，考虑到常见的暴露，我们假设作为第二种恶性肿瘤的基底细胞癌遗传易感性的生物标记物将不同于报道的发生病例的生物标记物。此外，儿童癌症幸存者中BCC的发生可能是辐射敏感度增加的人的一个标志。在这项研究中，我们将在病例对照比较中使用候选基因方法来探索预测儿童癌症幸存者患基底细胞癌风险的潜在生物标记物。我们将在两项后续研究中验证这项调查的积极观察结果，这两项研究检查了放射技术员和骨髓移植幸存者的基底细胞癌，以确定我们观察结果的概括性。这些验证研究超出了这笔赠款的工作范围，但将是将这一方法应用于更广泛人群的关键。我们为这项研究选择了候选基因方法，因为强有力的流行病学数据表明电离辐射是主要的危险因素，支持假设驱动的候选基因选择方法。 公共卫生相关性：儿童癌症幸存者罹患基底细胞癌(BCC)的风险很高，这是皮肤癌的一种，是放射治疗的长期副作用。一些幸存者在最初的癌症接受放射治疗后，可能在基因上容易患上基底细胞癌。对于这个研究项目，我们将开发一个预测模型，利用遗传学和治疗历史，潜在地帮助医生为每个患者量身定做治疗，以最大限度地减少辐射，如果孩子天生对辐射诱导的基底细胞癌敏感。

DESCRIPTION (provided by applicant): Survivors of childhood cancer have an increased risk of subsequent malignancy at another site. Previous studies in the Childhood Cancer Survivor Study (CCSS) have shown that the most frequent second malignant neoplasm is basal cell carcinoma (BCC), and that the most significant risk factor for BCC is exposure to therapeutic radiation. These data contrast with incident cases of BCC in the general population, for which the key risk factors are sun exposure and skin color. While it is clear that therapeutic radiation exposure increases risk of BCC in childhood cancer survivors, many are exposed to radiation and do not develop BCC. Thus, to address this inter- individual variation, given common exposures, we hypothesize that biomarkers of genetic susceptibility to BCC as a second malignancy will differ from those reported for incident cases. Furthermore, the occurrence of BCCs in childhood cancer survivors is potentially a marker of persons with increased radiation sensitivity. In this study, we will use a candidate gene approach in a case-control comparison to explore potential biomarkers that predict risk of BCC in childhood cancer survivors. We will validate positive observations from this investigation in two follow-up studies, which examine BCC in radiation technologists and bone marrow transplant survivors, to determine the generalizability of our observations. These validation studies are outside the work scope of this grant but will be key to the application of this approach to broader populations. We have selected a candidate gene approach for this study because the strong epidemiological data implicating ionizing radiation as the primary risk factor supports a hypothesis-driven approach to candidate gene selection. PUBLIC HEALTH RELEVANCE: Childhood cancer survivors have a high risk of developing basal cell carcinoma (BCC), a type of skin cancer, as a long-term side effect of radiation treatment. Some survivors may be genetically susceptible to developing BCC after receiving radiation treatment for their initial cancer. For this research project, we will develop a prediction model, using genetics and treatment history, to potentially help doctors tailor each patient's therapy to minimize radiation if the child has an innate susceptibility to radiation-induced BCC.